The invention relates to mass spectrometers having multiple ion optical assemblies and to means for positioning the multiple ion optical assemblies in the mass spectrometer. Mass spectrometry is a well-known technique for identifying the chemical composition of a sample based on the mass-to-charge (m/z) ratio of ions. Analyzing a sample using mass spectrometry generally consists of three steps: (a) formation of gas phase ions from sample, (b) mass analysis of the ions to separate the ions from one another according to ion mass, and (c) detection of the ions. Further functions may consist in guiding ions from the ion source to a mass analyzer, including a spatial and temporal shaping of guided stream of ions, or in fragmenting ions, for example by CID (collision induced dissociation) with background gas. These functions are performed by several methods and means existing in the field of mass spectrometry including ion optical assemblies, such as ion sources, RF (radio frequency) multipole ion guides, RF stacked ring ion guides, quadrupole mass filters, two- or three dimensional RF ion traps, DC focusing lenses and DC electrodes for guiding or accelerating ions, to name some examples.
The ion source assembly in a mass spectrometer is selected, for example, according to the chemical class of analytes to be ionized, the mass range of the analytes and the mass analyzer used for analyzing the ions. Commonly used ionization techniques are, for example, electron impact ionization (EI), chemical ionization (CI), matrix assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI). The different ion sources do not only differ in the ionization mechanism, but also in the pressure regime the ionization takes place. For example, an ESI source will almost always be operated at atmospheric pressure, whereas an EI source is operated at a lower pressure (in a medium to high vacuum). Other ion sources, like MALDI and CI, can be operated at different pressures ranging from atmospheric pressure up to pressures of medium vacuum (103 to 10−1 Pa), or in case of MALDI even in a high vacuum (10−1 to 10−7 Pa).
A mass analysis can be performed by a plurality of different mass analyzers, like time-of-flight mass analyzers, quadrupole mass filters, ion cyclotron resonance mass analyzers, magnetic and electric sector mass analyzers, RF quadrupole ion trap mass analyzer and electrostatic ion traps. Generally, mass analyzers operate in a high vacuum depending on the type of mass analyzer used.
Some very common mass spectrometers even comprise more than one mass analyzer. For example, time-of-flight mass analyzers with orthogonal ion injection (OTOF) are coupled to a quadrupole mass filter (Q) and a gas filled quadrupole collision cell (QqOTOF). In the case of a triple quadrupole mass spectrometer, one of the types of mass spectrometer most often sold, the mass spectrometer comprises three quadrupoles arranged in series. The first quadrupole (Q1) and the third quadrupole (Q3) act as quadrupole mass filters. The middle quadrupole (Q2) is a gas filled collision cell for inducing fragmentation of precursor ions selected in the first quadrupole. Subsequently, fragments are passed through to the third quadrupole where ions may be filtered or scanned fully. Since the quadrupole mass filters (Q1, Q3) are operated at high vacuum, whereas the quadrupole collision cell (Q2) is at medium vacuum pressure, the quadrupoles are frequently positioned in separate chambers (different vacuum stages) of the mass spectrometers. The ions are often transferred between these chambers by DC lenses gathering the ions at the end of a quadrupole and focusing them to the entrance of the adjacent quadrupole. However, there are triple quadrupole mass spectrometers in which all three quadrupoles are positioned in a single chamber (U.S. Pat. No. 6,576,897).
If the ions are generated in an ion source with an elevated pressure compared to the mass analyzer, the ions must be transported to the vacuum for mass analysis. In order for the gas phase ions to enter the mass analyzer, the ions must be separated from the background gas introduced by the operation of the ion source and transported through the single or multiple vacuum stages (compartments) of the mass spectrometer. The use of RF multipole ion guides has been shown to be an effective means for transporting ions, being generated in an ion source at atmospheric pressure and transferred into a low vacuum stage, from the low vacuum stage into high vacuum stages. Douglas et al. (U.S. Pat. No. 4,963,736) disclose a RF quadrupole ion guide that is used to transportions with high efficiency from a medium vacuum stage to a high vacuum stage with a quadrupole mass filter. Whitehouse et al. (U.S. Pat. No. 5,652,427) disclose RF multipole ion guides which begin in a first vacuum stage and extend continuously into one or more subsequent vacuum stages ending at the mass analyzer. In addition to being used for their transfer function, RF multipole devices known in the art, like RF multipole rod sets or RF stacked rings, can further be configured as gas collision cells for CID or as ion traps for fragmenting ions by ion-ion reactions, like ETD (electron transfer dissociation).
All ion optical assemblies of a mass spectrometer have to be precisely aligned with respect to each other in order to achieve a good performance for the whole mass spectrometer. The position accuracy between the ion optical assemblies can strongly affect the lower limit of detection and the mass resolution of the mass spectrometer, but also the mean time between maintenance. The latter is due to contaminations resulting from ion optical assemblies not being aligned in a proper way. The ion optical assemblies are often pre-assembled such that the components of the assemblies, like electrodes and supports, are precisely aligned with respect to each other.
In the prior art, like for example in the U.S. Pat. No. 6,797,948, the ion optical assemblies are aligned using aligning structures attached to the inside of the housing of the mass spectrometer, such as benches, to which all of the ion optical assemblies are mounted. However, these benches are unfavorable when the mass spectrometer comprises multiple vacuum stages and thus chambers, because the bench has either to be fed through the walls separating the chambers or has to be divided into multiple separated benches. The feedthroughs are disadvantageous due to the complexity of sealing the bench at the feedthroughs, whereas separated benches lose the advantage of having all ion optical assemblies aligned to the same bench, that is, the same frame of reference.
Ion optical assemblies of a mass spectrometer can further be aligned by attaching them to mounting means (separately manufactured holders and stands) which are again mounted on the inside of the housing of the mass spectrometer. Using mounting means has the disadvantage that there are multiple mechanical interfaces between the housing and the electrodes, as functional components of the ion optical assembly. A high number of interfaces results in a tolerance buildup that reduces the position accuracy of an ion optical assembly and the position accuracy between ion optical assemblies. The tolerance buildup can only be reduced by specifying the dimensions with very tight tolerances.
The U.S. Patent Application 2010/0327156 discloses another alternative for a precise alignment of ion optical assemblies. Here, the mass spectrometer comprises a housing with a panel wherein the panel is movable between an open and closed position relative to the housing. A first ion optical assembly is within the housing, while a second ion optical assembly is mounted to the panel. The ion optical assemblies are surrounded by the housing and the panel when the panel is in a closed position. An alignment mechanism aligns the first and second ion optical assemblies into a pre-determined alignment upon closing the panel.
Besides affecting the performance of the mass spectrometer, the alignment and mounting of the ion optical assemblies also affect the cost of production because this final assembly is time consuming and thus an expensive manufacturing step. It would be desirable to provide a mass spectrometer that can be assembled from pre-aligned ion optical assemblies rapidly while still maintaining high positional accuracy of the ion optical assemblies.